The DOI matches its Crossref record; 103 of the 105 references it cites were found in a registry or an index.
From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors
Abstract
Members of the B cell lymphoma 2 (BCL-2) gene family have a central role in regulating programmed cell death by controlling pro-apoptotic and anti-apoptotic intracellular signals. In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event; accordingly, selective inhibition of specific anti-apoptotic BCL-2 family proteins represents an exciting therapeutic opportunity. A combination of nuclear magnetic resonance (NMR)-based screening and structure-based drug design has yielded the first bona fide BCL-2 homology 3 (BH3) mimetics, including the BCL-2 and BCL-X L dual antagonist navitoclax, which is the first BCL-2 family inhibitor to show efficacy in patients with cancer. Clinical experience with navitoclax prompted the generation of the highly selective BCL-2 inhibitor venetoclax, which is now approved in the United States for the treatment of patients with chronic lymphocytic leukaemia with 17p deletion who have received at least one prior therapy. Recent advances have also been made in the development of potent and selective inhibitors of BCL-X L and myeloid cell leukaemia 1 (MCL1), which are additional BCL-2 family members with established anti-apoptotic roles in cancer. Here we review the latest progress in direct and selective targeting of BCL-2 family proteins for cancer therapy.
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In the citing paper
“Conversely, the BCL2 inhibitor venetoclax is currently available for the treatment of CLL patients who fail to obtain clinical benefit from conventional therapies [1046], and several other molecules with a similar mechanism of action are currently in clinical development [118] (source https://clinicaltrials.gov/).”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [1046]
In the citing paper
“The use of Bcl-xl inhibitors as senolytics is largely limited by their on-target and dose-limiting platelet toxicity.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [24]
In the citing paper
“Bcl-xl inhibition with ABT263 and other small molecular inhibitors induces platelet apoptosis and results in severe thrombocytopenia, which prevents the use of ABT263 and other Bcl-xl specific inhibitors in the clinic—even for cancer patients—because platelets solely depend on Bcl-xl for survival24–27.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [24]
In the citing paper
“ABT263 (also known as navitoclax), a Bcl-2 and Bcl-xl dual inhibitor23,24, is one of the most potent and broad-spectrum senolytic agents identified to date16–18.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [24]
In the citing paper
“Because both SCs and platelets, but not NCs, are primarily dependent on Bcl-xl for survival16–18,24–27 (Supplementary Fig. 1h), we evaluated the effects of PZ compared with ABT263 on the viability of WI38 NCs (Fig. 1g, left panel), IR-SCs (Fig. 1g, middle panel), and platelets (Fig. 1g, right panel).”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [24]
In the citing paper
“As reported, ABT263 was highly toxic to both WI38 IR-SCs (Fig. 1g, middle panel) and platelets16–18,24–27 (Fig. 1g, right panel; Supplementary Fig. 2).”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [24]
In the citing paper
“Therefore, PZ can selectively induce apoptosis in SCs, but not platelets, which are dependent on Bcl-xl for survival while having minimal toxicity to NCs that are less sensitive to Bcl-xl inhibition than SCs16–18,24–27.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [24]
In the citing paper
“the BCL2 inhibitor venetoclax has been approved by regulatory agencies for use in patients with CLL or small lymphocytic lymphoma (SLL) (Ashkenazi et al., 2017)”
From Immunomodulation by targeted anticancer agents (2021) · cites this paper as Ashkenazi et al., 2017
Citations
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics
Kerr, J. F. R., Wyllie, A. H., & Currie, A. R. (1972) · British Journal of Cancer · doi:10.1038/bjc.1972.33 · Cited by 15,673
Death Receptors: Signaling and Modulation
Ashkenazi, A., & Dixit, V. M. (1998) · Science · doi:10.1126/science.281.5381.1305 · Cited by 5,866
Self-citationDanial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
The landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017
An inhibitor of Bcl-2 family proteins induces regression of solid tumours
Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., Belli, B., Bruncko, M., Deckwerth, T. L., Dinges, J., Hajduk, P. J., et al. (2005) · Nature · doi:10.1038/nature03579 · Cited by 3,407
Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells
Vaux, D., Cory, S., & Adams, J. (1988) · Nature · doi:10.1038/335440a0 · Cited by 3,355
Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy
Czabotar, P. E., Lessene, G., Strasser, A., & Adams, J. M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3722 · Cited by 3,219
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets
Souers, A. J., Leverson, J. D., Boghaert, E. R., Ackler, S. L., Catron, N. D., Chen, J., Dayton, B. D., Ding, H., Enschede, S. H., Fairbrother, W. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3048 · Cited by 3,058
Self-citationDiscovering High-Affinity Ligands for Proteins: SAR by NMR
Shuker, S. B., Hajduk, P. J., Meadows, R. P., & Fesik, S. W. (1996) · Science · doi:10.1126/science.274.5292.1531 · Cited by 2,045
Research works printed but not linked: 1
- Seymour, J. F. et al. Reduction of tumor lysis syndrome (TLS) risk in chronic lymphocytic leukemia (CLL) patients treated with ABT-199 (GDC-0199): results of modifications to dosing schedule and TLS prophylaxis [abstract P868]. Haematologica 99 (Suppl. 1), 321 (2014).
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Small molecules in targeted cancer therapy: advances, challenges, and future perspectives
Zhong, L., Li, Y., Xiong, L., Wang, W., Wu, M., Yuan, T., Yang, W. M., Tian, C., Miao, Z., Wang, T., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00572-w · Cited by 1,813
Mitochondrial metabolism and cancer
Porporato, P. E., Filigheddu, N., Pedro, J. M. B., Kroemer, G., & Galluzzi, L. (2017) · Cell Research · doi:10.1038/cr.2017.155 · Cited by 1,323
NINJ1 mediates plasma membrane rupture during lytic cell death
Kayagaki, N., Kornfeld, O. S., Lee, B. L., Stowe, I. B., O’Rourke, K., Li, Q., Sandoval, W., Yan, D., Kang, J., Xu, M., et al. (2021) · Nature · doi:10.1038/s41586-021-03218-7 · Cited by 857
A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity
Khan, S., Zhang, X., Lv, D., Zhang, Q., He, Y., Zhang, P., Liu, X., Thummuri, D., Yuan, Y., Wiegand, J. S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0668-z · Cited by 688
Metadata
- Authors
- Ashkenazi, A., Fairbrother, W. J., Leverson, J. D., & Souers, A. J.
- Affiliations
- Genentech (US)
- AbbVie (United States) (US)
- Corresponding author
- Ashkenazi, Avi
- Venue
- Nature Reviews Drug Discovery
- Published
- 2017-02-17
- Volume
- 16
- Issue
- 4
- Pages
- 273-284
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W2589060305
- Cited by
- 903
- References
- 105
- Citations by year
- 2026: 49 · 2025: 87 · 2024: 99 · 2023: 90 · 2022: 94 · 2021: 120 · 2020: 116 · 2019: 93 · 2018: 100 · 2017: 51
- FWCI
- 9.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- Bcl-2 family proteins, apoptosis, BH3 mimetics, BCL-2 inhibitor, venetoclax, navitoclax, Bcl-xL, Mcl-1, small molecule inhibitors, structure-based drug design, NMR-based screening, apoptosis evasion, chronic lymphocytic leukemia, 17p deletion, cancer therapy
- MeSH terms
- Antineoplastic Agents, Humans, Neoplasms, Molecular Structure, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Protein Interaction Domains and Motifs, Molecular Targeted Therapy
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